A glycoconjugate in a cell plays an important role in the signal transduction and identification of cells, for example, identification of viruses, cancer cells and blood types, and clarification of sugar chain functions is considered as one of the targets of post-genome studies.
However, the method of synthesizing an oligonucleic acid and peptide has already been established, and is automated, but sugar chain synthesis method still contains many problems to be solved. Expectations are running high for establishment of sugar chain synthesis method and realization of an effective synthesizer in order to achieve successful clarification of sugar chain functions. At present, the following three sugar chain synthesis methods are practiced:                (1) Chemical synthesis        (2) Fermentation by genetically recombinant cell and microorganism        (3) Synthesis by glycosyltransferase.        
According to method (1), the targeted sugar chains are synthesized sequentially while protecting a hydroxyl group other than that for chemical bonding, and reaction steps are numerous and complicated. The method (2) provides a large volume of targeted sugar, but is accompanying by subsequent complicated purification process.
The method (3) was developed to solve the problems of methods (1) and (2). It includes the method disclosed in the Japanese Laid-Open Patent Publication No. Hei 11-42096. The method (3) uses the procedure of selective synthesis by glycosyltransferase, and does not require the process of protection of a hydroxyl group, as in method (1). Further, the amount of byproducts is smaller and the purification step subsequent to synthesis is facilitated.
In recent years, easy preparation of biologically active protein has been enabled by the development of genetic recombination technology. However, a great portion of biologically active protein is glycoprotein, and a sugar chain to be bonded is different according to each host. Activity may be seriously lost or damaged.
It will be very helpful if there is a way of reforming the changed sugar chain into the original one. Physiological function and activity are expected to be improved by modification into the sugar chain different from the originally bonded one. There are two methods of modifying the sugar chain of glycoprotein, and these methods are currently practiced.                (A) Fermentation by changing the host or using the host modified by injection of glycosyltransferase gene therein        (B) Fermentation of the obtained glycoprotein using endo- or exo-glycosidase and glycosyltransferase.        
According to method (A), the sugar chain to be bonded is changed but is not always changed into the desired one. To change the sugar chain into a specified one, method (B) is preferred. A method of using the transglycosylation of endoglycosidase includes the method disclosed in the Japanese Laid-Open Patent Publication No. Hei 05-64594. A method of using the transglycosylation of exo-glycosidase and glycosyltransferase includes the method disclosed in Eur. J. Biochem. 191:71-73 (1990).
However, these methods modify only the sugar residues of the non-reducing terminus at most, and fail to bring about full-scale modification of sugar chains. There is a further way of using endoglycosidase and glycosyltransferase. For example, there is a method disclosed in J. Am. Chem. Soc. 119:2114-2118 (1997). In this method, glycosyltransferase is used to extend sugar chains onto the non-reducing terminus of the N-acetyl glucosamine residue remaining on the protein subsequent to hydrolysis by endoglycosidase, thereby promoting modification into the glycoprotein bonded with sialyl Lewis×tetraose. The sugar chain bonded is the non-reducing terminus portion of the sugar chain of glycoprotein, and this method is insufficient to achieve modification of the entire sugar chain.
A sugar chain synthesizer is disclosed in the Japanese Laid-Open International Patent Publication No. Hei 05-500905.